Anatomy of CD1-lipid antigen complexes

Abstract

CD1 proteins bind lipids to form antigen complexes that contact T-cell receptors and activate T cells. Recent crystal structures of CD1 proteins show that their antigen-binding grooves are composed of up to four pockets (A', C', F' and T') and two antigen portals (C' and F'). Although certain structural features are conserved among CD1 proteins, the grooves of CD1a, CD1b and CD1d differ in the number, shape and connectivity of their antigen-binding pockets. Here, we outline how the portals and pockets of CD1 antigen-binding grooves influence ligand specificity and facilitate the presentation of a surprisingly diverse set of antigenic lipids, glycolipids, lipopeptides and even small, non-lipidic molecules.